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BJA Advance Access published online on October 1, 2004
British Journal of Anaesthesia, doi:10.1093/bja/aeh278
© 2004 by The Board of Management and Trustees of the British Journal of Anaesthesia
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Accepted August 4, 2004

Laboratory Investigation

Pulmonary vasodilator effects of norepinephrine during the development of chronic pulmonary hypertension in neonatal lambs

S. Jaillard 1, F. Elbaz 2, S. Bresson-Just 3, Y. Riou 4, V. Houfflin-Debarge 4, T. Rakza 3, B. Larrue 2, and L. Storme 5*

1 Department of Anesthesiology and Cardio-thoracic Surgery, Centre Hospitalier et Universitaire, Lille, France; EA1049, Department of Biophysics, Centre Hospitalier et Universitaire, Lille, France; Departement Hospitalo-Universitaire de Recherche Experimentale, Centre Hospitalier et Universitaire, Lille, France
2 Department of Anesthesiology and Cardio-thoracic Surgery, Centre Hospitalier et Universitaire, Lille, France
3 Department of Perinatal Medicine, Centre Hospitalier et Universitaire, Lille, France
4 Department of Perinatal Medicine, Centre Hospitalier et Universitaire, Lille, France; EA1049, Department of Biophysics, Centre Hospitalier et Universitaire, Lille, France
5 Department of Perinatal Medicine, Centre Hospitalier et Universitaire, Lille, France; EA1049, Department of Biophysics, Centre Hospitalier et Universitaire, Lille, France; Departement Hospitalo-Universitaire de Recherche Experimentale, Centre Hospitalier et Universitaire, Lille, France

* To whom correspondence should be addressed. E-mail: lstorme{at}chru-lille.fr.


  Abstract

Background. This experimental study was performed to determine the effects of norepinephrine on: (i) the pulmonary vascular tone during the development of pulmonary hypertension (PH) in the fetus and (ii) the circulatory adaptation at birth after chronic intrauterine PH.

Methods. Chronically instrumented fetal lambs were randomized into two groups: (i) a group with PH obtained by antenatal partial ligation of the ductus arteriosus (DA) (n=9) and (ii) a control group without DA ligation (n=6). Pulmonary vascular responses to norepinephrine (1.5 µg min-1) were measured in utero 7 days after surgery. At day 8 post-surgery, after delivery, animals were ventilated for 3 h with oxygen 100%. The group with PH was randomly assigned to receive norepinephrine or saline.

Results. Mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were higher in the PH group (P<0.01). Norepinephrine-induced decrease in PVR was more pronounced in the PH group than in the control group (63 vs 35%, respectively; P<0.01). In the PH group, the decrease in PVR during mechanical ventilation was greater in the animals receiving norepinephrine than in the animal receiving saline (from 1.05 (0.12) to 0.1 (0.02) vs from 1.04 (0.1) to 0.2 (0.04) mm Hg ml-1 min-1, respectively; P<0.01). After 3 h of ventilation, mean PVR in the PH lambs treated by norepinephrine was similar to those measured in the control lambs. Aortic pressure was higher in the group treated with norepinephrine.

Conclusion. The data suggest that norepinephrine may improve post-natal pulmonary adaptation in the newborn with persistent PH both by increasing systemic vascular pressure and by increasing pulmonary blood flow.

Keywords: arteries, small pulmonary arteries; complications, pulmonary hypertension; pharmacology, nitric oxide; sympathetic nervous system, norepinephrine.
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